Neoplastic cells and rapidly dividing normal cells are more effectively protected against in vitro lipid peroxidation processes than are slowly dividing normal cells, by antioxidants such as vitamin E, selenium, thiol compounds and certain protein factors. In the precancerous state, antioxidants function as protective agents by inhibiting certain cellular processes involved in oncogenesis. However, once the neoplasm is established the cancer cell appears to use its enhanced antioxidant status to the disadvantage of the host. In cancers, antioxidants may have the following effects: a) enhance mitotic potential by influencing nuclear thiol levels; b) decrease the susceptibility to radiation therapy; c) decrease the susceptibility to certain therapeutic agents. It is our general goal to study the nature of the enhanced antioxidant protective mechanism in cancer cells, particularly the unique cofactor requirement by vitamin E in NAD-induced inhibition of mitochondrial respiration. It is our aim to reduce this antioxidant protective effect in order to enhance the susceptibility of cancer cells to various therapeutic modalities mentioned above.